Apolipoprotein E (apoE), a 34,000 molecular weight protein, is the product of a single gene on chromosome 19 and exists in three major isoforms designated apoE2, apoE3 and apoE4. ApoE mRNA is abundant in the brain, where it is synthesized and secreted primarily by astrocytes. Although apoE is synthesized in the brain primarily by astrocytes, neurons in the central nervous system (CNS) express apoE in response to excitotoxic stress and other insults. It has been shown that neuronal expression of apoE, especially apoE4, contributes to the pathogenesis of Alzheimer's Disease (AD), such as neurofibrillary tangle formation and mitochondrial dysfunction. However, the molecular mechanisms underlying the regulation of neuronal expression of apoE are poorly understood.
There are currently no effective therapies for arresting (and, more importantly, reversing) the impairment of central and peripheral nervous system function once an irreversible degenerative cascade begins. Likewise, there is no current therapy for restoration of normal, central and peripheral nervous system function when the induced stress has a less catastrophic or partially reversible effect compared to the dementias. There is a need in the art for effective therapies for treating disorders associated with apoE.
Literature
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